The Role of Community Engagement in Successful Recruitment of Research Participants During the COVID-19 Pandemic.

Background: Our research team was in the process of recruiting American Indian and Alaska Native (AIAN) women for a community-based intervention to prevent alcohol-exposed pregnancy when the COVID-19 pandemic began. Safety measures adopted at the tribal, state, and national level required us to rethink and revise study protocols. We followed the principles of community-based participatory research, especially community engagement. The goal of this article is to report the recommendations from local AIAN field staff and the community advisory board that enabled us to exceed our prepandemic recruitment goal. Methods: First, we developed a list of major adaptations and mapped each one onto our recruitment timeline to assess its effect on subsequent enrollment. Second, we surveyed the two AIAN field staff who led recruitment and an administrative staffer at the study site and conducted a qualitative analysis of their responses. Results: Our revised project timeline presents the major adaptations that led to our successful recruitment, as verified by qualitative data from field staff. These adaptations included expanding our social media presence, expanding recruitment to a nearby urban site, implementing a "refer a friend" program, and recruiting through local media outlets. Most important was having local AIAN staff who cultivated a nonjudgmental space for potential participants to talk about sensitive topics. Discussion: We not only met our prepandemic recruitment goal but exceeded it by 16.6%. The input of our community advisory board and the efforts of community-based staff were essential in achieving success during the unprecedented conditions of the COVID-19 pandemic.

Multielectrode array characterization of human induced pluripotent stem cell derived neurons in co-culture with primary human astrocytes.

Human induced pluripotent stem cells (hiPSCs) derived into neurons offer a powerful in vitro model to study cellular processes. One method to characterize functional network properties of these cells is using multielectrode arrays (MEAs). MEAs can measure the electrophysiological activity of cellular cultures for extended periods of time without disruption. Here we used WTC11 hiPSCs with a doxycycline-inducible neurogenin 2 (NGN2) transgene differentiated into neurons co-cultured with primary human astrocytes. We achieved a synchrony index ∼0.9 in as little as six-weeks with a mean firing rate of ∼13 Hz. Previous reports show that derived 3D brain organoids can take several months to achieve similar strong network burst synchrony. We also used this co-culture to model aspects of blood-brain barrier breakdown by using human serum. Our fully human co-culture achieved strong network burst synchrony in a fraction of the time of previous reports, making it an excellent first pass, high-throughput method for studying network properties and neurodegenerative diseases.

Knowledge translation strategies used to promote evidence-based interventions for children with cerebral palsy: a scoping review.

BACKGROUND: Cerebral palsy (CP) is the most common childhood physical disability, imposing substantial costs on individuals and society. Early interventions that promote brain optimization and reorganization are vital for children with CP. Integrating early evidence-based practice (EBP) remains challenging but enhances functional outcomes. METHODS: Following a scoping review methodology, databases were searched to identify studies examining the impact of knowledge translation (KT) strategies for pediatric CP interventions. Extraction included study characteristics, methodology, KT strategies, barriers, and facilitators. Numerical and inductive content analysis identified themes among KT strategies. A final stakeholder consultation to discuss the results was conducted. RESULTS: This review included seventeen articles. Common outcomes included participant change in EBP knowledge and behaviour. Common barriers included a need for more resources, protected time, and funding. Most studies followed a multifaceted KT approach. Various KT strategies were used, primarily mentoring, workshops, case studies, and online tools. INTERPRETATION: Results underscored the need for tailored KT strategies for implementing EBP for children with CP. Additionally, user-friendly KT tools and involving mentors to facilitate the intervention can haste EBP uptake. Successful adoption depends on challenges in healthcare settings. This study provides insights into current KT strategies for advancing best practices for children with CP.

Employing multifaceted knowledge translation strategies in a pediatric rehabilitation setting can support the adoption of evidence-based practices for children with cerebral palsy.It is important to identify and address common barriers hindering the use of evidence-based practices in cerebral palsy rehabilitation in a specific context to tailor a knowledge translation strategy.Having qualified rehabilitation professionals act as evidence-based practice leaders in a healthcare setting is crucial for promoting evidence-based practices among other professionals.

Reach, Acceptability, and Sustainability of the Native Changing High-Risk Alcohol Use and Increasing Contraception Effectiveness Study (CHOICES) Intervention: A Qualitative Evaluation of an Alcohol-Exposed Pregnancy Prevention Program.

American Indian (AI) women are at risk of alcohol-exposed pregnancy (AEP) due to the higher prevalence of alcohol use disorders (AUDs) and risky drinking. The Native Changing High-Risk Alcohol Use and Increasing Contraception Effectiveness Study (Native CHOICES) was implemented in partnership with a Northern Plains Tribal community to address the effectiveness of a brief, motivational interviewing-based intervention to reduce AEP risk among adult AI women. A subgroup of the participants shared their perspectives in a qualitative interview conducted following the completion of the six-month post-baseline data collection. These interviews solicited participant perspectives on the Native CHOICES intervention and its satisfaction, reach, acceptability, and sustainability. The participants were delighted with Native CHOICES, felt the intervention helped them learn about AEP prevention and goal setting, learned valuable lessons, and believed Native CHOICES would be well-received by other women in their community and should be continued. The participants also shared how the COVID-19 pandemic affected their choices about drinking and birth control. The findings showed the receptivity to and acceptance of Native CHOICES among AI women. The interview findings offered a glimpse into the effectiveness of Native CHOICES and how it contributed to participants making healthier choices surrounding drinking and sexual health.

Mental health in children with disabilities and their families: red flags, services' impact, facilitators, barriers, and proposed solutions.

Background: Children and youth with neurodevelopmental disabilities (NDDs) and their caregivers are at a high risk of experiencing mental health challenges, that in turn can significantly affect their functioning, productivity, and quality of life. In this already vulnerable population, mental health difficulties are now more frequently reported and pronounced secondary to the isolation and uncertainties experienced during the pandemic. Our previous work has shown important mental health services' gaps for children/youth with NDDs and their families, highlighting the need to optimize and tailor existing practices. Objective: To explore mental health services' barriers, facilitators, impact, and solutions from the perspectives of HCPs and CGs, and to describe common precursors to mental health challenges in children with NDDs from the perspectives of these two groups. Methods: In a triangulation mixed-method study design embedding quantitative and qualitative approaches, participants completed a survey and a semi-structured interview. Descriptive statistics and a hybrid inductive/deductive thematic approach were used for data analysis. Results: Over 700 utterances were analyzed (247 from caregivers [n = 10], 531 from clinicians [n = 16]) and included 143 and 173 statements related to the precursors and barriers/facilitators, respectively. Common precursors to mental health challenges (n = 7 categories) were identified and included reported feelings/perception of self, behavioral and physical manifestations, emotional dysregulation, and school-related factors, among others. Clinicians reported a widespread need for pediatric, family-centered mental health services and conveyed lacking mental health resources/training to meet the demand. Caregivers indicated being only moderately satisfied when care was received. Salient facilitators identified by clinicians were having an interdisciplinary team and caregiver's engagement in the therapeutic processes. Participants recommended improvements to increase accessibility to mediate the existing discrepancy between the emergence of precursors and care received; that services must target a broader population and be more comprehensive (e.g., family-centered care, addressing high-risk transition periods); and training/toolkits to support clinicians' evidence-based practice. Conclusion: Our findings emphasize the necessity of a systematic and standardized approach to mental health services for children with NDDs and their families. Enhancing caregiver support, addressing barriers, and adopting a proactive, family-centered approach are crucial for improving accessibility and quality. These proposed solutions provide valuable insights for shaping policies and practices in pediatric mental health services.

"Sorry for laughing, but it's scary": humor and silence in discussions of Colorectal Cancer with Urban American Indians.

BACKGROUND: Given high rates of cancer mortality in Native communities, we examined how urban American Indian and Alaska Native elders talk about colorectal cancer (CRC) and CRC screening. METHODS: We conducted seven focus groups with a total of 46 participants in two urban clinics in the Pacific Northwest to assess participant awareness, perceptions, and concerns about CRC and CRC screening. Using speech codes theory, we identified norms that govern when and how to talk about CRC in this population. RESULTS: Our analyses revealed that male participants often avoided screening because they perceived it as emasculating, whereas women often avoided screening because of embarrassment and past trauma resulting from sexual abuse. Both men and women used humor to mitigate the threatening nature of discussions about CRC and CRC screening. CONCLUSIONS: We offer our analytic results to assist others in developing culturally appropriate interventions to promote CRC screening among American Indians and Alaska Natives.

Id2 GABAergic interneurons comprise a neglected fourth major group of cortical inhibitory cells.

Cortical GABAergic interneurons (INs) represent a diverse population of mainly locally projecting cells that provide specialized forms of inhibition to pyramidal neurons and other INs. Most recent work on INs has focused on subtypes distinguished by expression of Parvalbumin (PV), Somatostatin (SST), or Vasoactive Intestinal Peptide (VIP). However, a fourth group that includes neurogliaform cells (NGFCs) has been less well characterized due to a lack of genetic tools. Here, we show that these INs can be accessed experimentally using intersectional genetics with the gene Id2. We find that outside of layer 1 (L1), the majority of Id2 INs are NGFCs that express high levels of neuropeptide Y (NPY) and exhibit a late-spiking firing pattern, with extensive local connectivity. While much sparser, non-NGFC Id2 INs had more variable properties, with most cells corresponding to a diverse group of INs that strongly expresses the neuropeptide CCK. In vivo, using silicon probe recordings, we observed several distinguishing aspects of NGFC activity, including a strong rebound in activity immediately following the cortical down state during NREM sleep. Our study provides insights into IN diversity and NGFC distribution and properties, and outlines an intersectional genetics approach for further study of this underappreciated group of INs.

The use of patient navigation to transition detoxification patients to substance use treatment in the Alaska Interior.

Objectives: Detoxification clinics manage acute intoxication and withdrawal from alcohol and other drugs. At discharge, patients are referred to treatment, yet many are readmitted to detoxification, creating a "revolving door" of discharges and admissions. This pattern disproportionately affects some groups such as Alaska Native and American Indian (AN/AI) people. The primary goals of this study are to: 1) test the effectiveness of a patient navigation intervention to increase rates of transition to alcohol treatment following detoxification, and 2) prevent readmission to detoxification within 12-months. The secondary goal is a cost-effectiveness and cost-benefit evaluation of patient navigation. Study design: This randomized controlled comparative effectiveness trial plans to recruit 440 patients (∼70% AN/AI) admitted to alcohol detoxification. We collaborated with Fairbanks Native Association (FNA) to select an appropriate intervention, control condition, and other study-related decisions. Here, we describe intervention development, study design, challenges encountered during implementation, and collaborative processes to identify solutions. Methods: Participants are equally randomized to the control (one motivational interviewing session) or intervention (one motivational interviewing session plus up to four weeks of patient navigation). The primary outcomes are successful transition to alcohol treatment within 30-days after discharge and detoxification readmission within 12-months. The secondary outcome is health-related quality of life. Conclusion: Patient navigation is successful in other settings and for other health conditions. It may assist in overcoming barriers to successful transition to substance use treatment and may augment interventions, such as motivational interviewing, that are less resource-intensive but may not be optimally effective by themselves. ClinicalTrialsgov Identifier: NCT03737864.

Mental health services and resources for children with developmental disabilities and their families: scan of local practices, gaps, and opportunities created.

Background: Mental health concerns in children with disabilities are common and have a significant and negative impact. Clinicians have reported high demand for this population to receive early, targeted, and family-centred mental health interventions. Objective: We sought to map out and describe existing pediatric mental health services/resources for children with disabilities and their families across clinical sites and local and online communities. Methods: Using a mixed-method triangulation study design, we outreached to clinical managers at the participating clinical sites and conducted a rapid online search of local in-person, telehealth, and web-based information. The nature, access method, admission criteria, target, focus, and other pertinent information were recorded and analyzed using descriptive statistics and a narrative synthesis approach. Results: Eighty-one (n = 81) services/resources (in-person, n = 48; telehealth, n = 10; web-based information, n = 33) were identified. Few (n = 6, 13%) in-person services had a method of care access through an online booking portal. Nearly half of in-person resources (n = 23, 47%) had admission criteria specific for children with disabilities (e.g., diagnosis, age limit), and many (n = 32, 67%) required a formal referral. A small number of in-person and telehealth services targeted the mental health concerns of the entire family (n = 23, 47%; n = 2, 20%). Very few (n = 13, 16%) services incorporated follow-up support. Important gaps emerged for certain populations (e.g., children with cerebral palsy). Practitioners' inadequate training when intervening with co-existing mental health demands of children with disabilities was noted by clinical managers. Conclusion: Findings could be used to create a user-friendly database to easily identify suitable services and to advocate for services/resources that are lacking.

Feasibility and Acceptability of Using Ecological Momentary Assessment to Evaluate Alcohol Use with American Indian Women.

BACKGROUND: Ecological momentary assessments (EMA) are one way to collect timely and accurate alcohol use data, as they involve signaling participants via cell phones to report on daily behaviors in real-time and in a participant's natural environment. EMA has never been used with American Indian populations to evaluate alcohol consumption. The purpose of this project was to determine the feasibility and acceptability of EMA for American Indian women. METHODS: Eligible participants were American Indian women between the ages of 18 and 44 who were not pregnant and had consumed more than one drink within the past month. All participants received a TracFone and weekly automated messages. Self-reported measures of daily quantity and frequency of alcohol consumption, alcohol type, and context were assessed once per week for four weeks. Baseline measurements also included the Drinking Motives Questionnaire-Revised (DMQ-R) and the Interpersonal Support Evaluation List (ISEL). RESULTS: Fifteen participants were enrolled in the study. All but one participant completed all data collection time points, and drinking patterns were consistent across the study period. A total of 420 records were completed across 86 drinking days and 334 non-drinking days. Participants reported drinking an average of 5.7 days over the 30-day period and typically consumed 3.99 drinks per drinking occasion. Sixty-six percent of participants met gender-specific cut-points for heavy episodic drinking, with an average of 2.46 binge drinking occasions across the four week study period. CONCLUSIONS: This proof-of-concept project showed that EMA was both feasible and acceptable for collecting alcohol data from American Indian women. Additional studies are necessary to fully implement EMA with American Indian women to better understand the drinking motives, contexts, patterns, and risk factors in this population.

Alcohol consumption and pregnancy in American Indian and Alaska Native women: A scoping review of the literature.

American Indian and Alaska Native communities have diverse cultures, histories, and contemporary experiences. Grouping them together masks the differences in health and lifestyle behaviors, chronic disease rates, and health outcomes among them. This is particularly true for data on drinking during pregnancy among American Indian and Alaska Native women. The goal of this article is to describe how generalizing findings from data gathered from often small, geographically specific samples, combined with inferior research methodologies, has led to misunderstandings about drinking among preconceptual and pregnant American Indian and Alaska Native women. We conducted a scoping review using PubMed and the "PCC mnemonic" (population, concept, and context) as our guide. Our search terms included the population (American Indian and Alaska Native women), concept (alcohol), and context (immediately before or during pregnancy) and focused on PubMed articles in the United States. Using these search terms, we uncovered a total of 38 publications and eliminated 19, leaving 19 for review. Methodologically (i.e. how data were collected), we found most previous research on prenatal or preconceptual alcohol use with American Indian and Alaska Native women used retrospective data collection. We also assessed who data were collected from and noted two groups: studies that sampled higher-risk women and those that focused on American Indian and Alaska Native women in specific geographic areas. Restricting data collection to higher-risk American Indian and Alaska Native women or conducting small studies in specific geographic areas has generated an incomplete and inaccurate picture of American Indian and Alaska Native women as a whole as well as those who consume alcohol. Data from select groups of American Indian and Alaska Native women may overestimate the true prevalence of drinking during pregnancy among this population. Updated and accurate data on drinking during pregnancy are urgently needed to inform the development of interventions and prevention efforts.

Pediatric tele-coaching fidelity evaluation: Feasibility, perceived satisfaction and usefulness of a new measure.

Background: To promote and ensure coaches' fidelity in delivering an online health coaching program to parents of children with suspected developmental delay, we developed and implemented a novel coaching fidelity rating tool, CO-FIDEL (COaches Fidelity in Intervention DELivery). We aimed to (1) Demonstrate CO-FIDEL's feasibility in evaluating coaches' fidelity and its change over time; and (2) Explore coaches' satisfaction with and usefulness of the tool. Methods: In an observational study design, coaches (n = 4) were assessed using the CO-FIDEL following each coaching session (n = 13-14 sessions/parent-participant) during the pilot phase of a large randomized clinical trial involving eleven (n = 11) parent-participants. Outcome measures included subsections' fidelity measures, overall coaching fidelity, and coaching fidelity changes over time analyzed using descriptive and non-parametric statistics. In addition, using a four-point Likert Scale and open-ended questions, coaches were surveyed on their satisfaction and preference levels, as well as facilitators, barriers, and impacts related to the use of CO-FIDEL. These were analyzed using descriptive statistics and content analysis. Results: One hundred and thirty-nine (n = 139) coaching sessions were evaluated with the CO-FIDEL. On average, overall fidelity was high (88.0 ± 6.3 to 99.5 ± 0.8%). Four coaching sessions were needed to achieve and maintain a ≥ 85.0% fidelity in all four sections of the tool. Two coaches showed significant improvements in their coaching skills over time in some of the CO-FIDEL sections (Coach B/Section 1/between parent-participant B1 and B3: 89.9 ± 4.6 vs. 98.5 ± 2.6, Z = -2.74, p = 0.00596; Coach C/Section 4/between parent-participant C1 and C2: 82.4 ± 7.5 vs. 89.1 ± 4.1, Z = -2.66; p = 0.00758), and in overall fidelity (Coach C, between parent-participant C1 and C2: 88.67 ± 6.32 vs. 94.53 ± 1.23, Z = -2.66; p = 0. 00758). Coaches mainly reported moderate-high satisfaction with and usefulness of the tool, and pointed out areas of improvement (e.g., ceiling effect, missing elements). Conclusions: A new tool ascertaining coaches' fidelity was developed, applied, and shown to be feasible. Future research should address the identified challenges and examine the psychometric properties of the CO-FIDEL.

UBQLN2 restrains the domesticated retrotransposon PEG10 to maintain neuronal health in ALS.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron dysfunction and loss. A portion of ALS cases are caused by mutation of the proteasome shuttle factor Ubiquilin 2 (UBQLN2), but the molecular pathway leading from UBQLN2 dysfunction to disease remains unclear. Here, we demonstrate that UBQLN2 regulates the domesticated gag-pol retrotransposon 'paternally expressed gene 10 (PEG10)' in human cells and tissues. In cells, the PEG10 gag-pol protein cleaves itself in a mechanism reminiscent of retrotransposon self-processing to generate a liberated 'nucleocapsid' fragment, which uniquely localizes to the nucleus and changes the expression of genes involved in axon remodeling. In spinal cord tissue from ALS patients, PEG10 gag-pol is elevated compared to healthy controls. These findings implicate the retrotransposon-like activity of PEG10 as a contributing mechanism in ALS through the regulation of gene expression, and restraint of PEG10 as a primary function of UBQLN2.

Peripheral T-Cell Lymphoma in a Patient Previously Diagnosed With Sarcoidosis.

Sarcoidosis is a multisystem disorder characterized by granulomatous inflammation on histopathological evaluation. Diagnosis of sarcoidosis requires thorough elimination of malignancy and alternative causes of noncaseating granulomatous inflammation. Sarcoidosis and several subtypes of lymphoma have similar clinical presentations and can potentially have similar histopathological findings. Patients with a histopathology-confirmed diagnosis of sarcoidosis are at higher risk of developing malignancies. In this report, we present a case of a 64-year-old male diagnosed with sarcoidosis 2 years before presenting to the emergency department with a 4-month history of generalized weakness, cough, and very high fever. After a thorough workup involving cervical lymph node biopsy and bone marrow biopsy, he was diagnosed with peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS). Due to the patient's current lymphoma diagnosis and features noted on pathology, a retrospective review of the prior biopsy specimen was performed, finding similar hematopathological features on both initial lymph node biopsy diagnosing sarcoidosis and current biopsies diagnosing lymphoma. Given these findings, our patient likely had early manifestation of PTCL misdiagnosed as sarcoidosis. In summary, lymphoma should be considered in all patients with suspected sarcoidosis, especially those who do not respond to treatment or who present with persistent hematological abnormalities.

Identifying an Optimal Neuroinflammation Treatment Using a Nanoligomer Discovery Engine.

Acute activation of innate immune response in the brain, or neuroinflammation, protects this vital organ from a range of external pathogens and promotes healing after traumatic brain injury. However, chronic neuroinflammation leading to the activation of immune cells like microglia and astrocytes causes damage to the nervous tissue, and it is causally linked to a range of neurodegenerative diseases such as Alzheimer's diseases (AD), Multiple Sclerosis (MS), Parkinson's disease (PD), and many others. While neuroinflammation is a key target for a range of neuropathological diseases, there is a lack of effective countermeasures to tackle it, and existing experimental therapies require fairly invasive intracerebral and intrathecal delivery due to difficulty associated with the therapeutic crossover between the blood-brain barrier, making such treatments impractical to treat neuroinflammation long-term. Here, we present the development of an optimal neurotherapeutic using our Nanoligomer Discovery Engine, by screening downregulation of several proinflammatory cytokines (e.g., Interleukin-1ß or IL-1ß, tumor necrosis factor-alpha or TNF-α, TNF receptor 1 or TNFR1, Interleukin 6 or IL-6), inflammasomes (e.g., NLRP1), key transcription factors (e.g., nuclear factor kappa-B or NF-κß) and their combinations, as upstream regulators and canonical pathway targets, to identify and validate the best-in-class treatment. Using our high-throughput drug discovery, target validation, and lead molecule identification via a bioinformatics and artificial intelligence-based ranking method to design sequence-specific peptide molecules to up- or downregulate gene expression of the targeted gene at will, we used our discovery engine to perturb and identify most effective upstream regulators and canonical pathways for therapeutic intervention to reverse neuroinflammation. The lead neurotherapeutic was a combination of Nanoligomers targeted to NF-κß (SB.201.17D.8_NF-κß1) and TNFR1 (SB.201.18D.6_TNFR1), which were identified using in vitro cell-based screening in donor-derived human astrocytes and further validated in vivo using a mouse model of lipopolysaccharide (LPS)-induced neuroinflammation. The combination treatment SB_NI_111 was delivered without any special formulation using a simple intraperitoneal injection of low dose (5 mg/kg) and was found to significantly suppress the expression of LPS-induced neuroinflammation in mouse hippocampus. These results point to the broader applicability of this approach towards the development of therapies for chronic neuroinflammation-linked neurodegenerative diseases, sleep countermeasures, and others, and the potential for further investigation of the lead neurotherapeutic molecule as reversible gene therapy.

Adaptations of an RCT during COVID: Case Study in one Rural American Indian Community.

The COVID-19 pandemic is global in nature but especially threatens American Indian and Alaska Native (AI/AN) communities due to pre-existing conditions and social determinants of health. Because of the higher risk to AI/AN communities, many tribal nations have been proactive in their policies to keep the virus at bay, including travel restrictions and lockdowns. This affected tribal programs as well as collaborative research projects. One project impacted is the Native CHOICES project, an ongoing randomized controlled trial with an AI/AN community that is focused on the prevention of alcohol-exposed pregnancies. Originally designed to be conducted via in-person motivational interviewing sessions, COVID-19 restrictions precluded the intervention from being delivered in-person as it was designed. The study team received valuable input from the project's Community Advisory Board (CAB) and community-based staff to establish a feasible and acceptable way of conducting the intervention while respecting tribally-enacted COVID-19 restrictions. The goal of this brief report is to outline not just the process to adapting to COVID-19 but also to provide recommendations for future public health programs, including the ongoing need to consider gaps in access affecting resource-poor settings.

RCAN1 knockout and overexpression recapitulate an ensemble of rest-activity and circadian disruptions characteristic of Down syndrome, Alzheimer's disease, and normative aging.

BACKGROUND: Regulator of calcineurin 1 (RCAN1) is overexpressed in Down syndrome (DS), but RCAN1 levels are also increased in Alzheimer's disease (AD) and normal aging. AD is highly comorbid among individuals with DS and is characterized in part by progressive neurodegeneration that resembles accelerated aging. Importantly, abnormal RCAN1 levels have been demonstrated to promote memory deficits and pathophysiology that appear symptomatic of DS, AD, and aging. Anomalous diurnal rest-activity patterns and circadian rhythm disruptions are also common in DS, AD, and aging and have been implicated in facilitating age-related cognitive decline and AD progression. However, no prior studies have assessed whether RCAN1 dysregulation may also promote the age-associated alteration of rest-activity profiles and circadian rhythms, which could in turn contribute to neurodegeneration in DS, AD, and aging. METHODS: The present study examined the impacts of RCAN1 deficiency and overexpression on the photic entrainment, circadian periodicity, intensity and distribution, diurnal patterning, and circadian rhythmicity of wheel running in young (3-6 months old) and aged (9-14 months old) mice of both sexes. RESULTS: We found that daily RCAN1 levels in the hippocampus and suprachiasmatic nucleus (SCN) of light-entrained young mice are generally constant and that balanced RCAN1 expression is necessary for normal circadian locomotor activity rhythms. While the light-entrained diurnal period was unaltered, RCAN1-null and RCAN1-overexpressing mice displayed lengthened endogenous (free-running) circadian periods like mouse models of AD and aging. In light-entrained young mice, RCAN1 deficiency and overexpression also recapitulated the general hypoactivity, diurnal rest-wake pattern fragmentation, and attenuated amplitudes of circadian activity rhythms reported in DS, preclinical and clinical AD, healthily aging individuals, and rodent models thereof. Under constant darkness, RCAN1-null and RCAN1-overexpressing mice displayed altered locomotor behavior indicating circadian clock dysfunction. Using the Dp(16)1Yey/+ (Dp16) mouse model for DS, which expresses three copies of Rcan1, we found reduced wheel running activity and rhythmicity in both light-entrained and free-running young Dp16 mice like young RCAN1-overexpressing mice. Critically, these diurnal and circadian deficits were rescued in part or entirely by restoring Rcan1 to two copies in Dp16 mice. We also found that RCAN1 deficiency but not RCAN1 overexpression altered protein levels of the clock gene Bmal1 in the SCN. CONCLUSIONS: Collectively, this study's findings suggest that both loss and aberrant gain of RCAN1 precipitate anomalous light-entrained diurnal and circadian activity patterns emblematic of DS, AD, and possibly aging.

Factors associated with readmission to alcohol and opioid detoxification in the Alaska Interior.

BACKGROUND AND OBJECTIVES: A "revolving door" of repeated admissions to detoxification treatment facilities has long plagued alcohol and drug use patients, yet few studies examine factors associated with readmission. This study examined risk factors for readmission to alcohol and opioid detoxification in a sample from the Alaska Interior. METHODS: Data were extracted from electronic medical records for admissions between 2012 and 2016 at an inpatient detoxification facility in Fairbanks, Alaska. Data from 1014 patients admitted for alcohol detoxification and 267 patients admitted for opioid detoxification were analyzed. The analysis employed descriptive statistics for risk factors (substance use history, adverse life experiences, and psychosocial functioning) and prevalence of readmission to either alcohol or opioid detoxification. Inferential analyses used marginal standardization to calculate differences in readmission risk by patient characteristics. RESULTS: Male, Alaska Native/American Indian, single-never married patients, and those seeking work were at higher risk for readmission to alcohol detoxification, while those with stable housing were at reduced risk. Being single-never married and completing detoxification treatment reduced readmission to opioid detoxification. Family involvement in detoxification reduced readmission risk for both alcohol and opioid patients. DISCUSSION AND CONCLUSIONS: Further research that investigates the mechanism(s) by which family may act as a protective factor may be efficacious in eliminating the "revolving door" of detoxification. SCIENTIFIC SIGNIFICANCE: This study is the first to examine both alcohol and opioid use risk and protective factors in the Alaska Interior. The results can be used in the development of interventions for subpopulations with high detoxification readmission rates.

Preconception interventions to reduce the risk of alcohol-exposed pregnancies: A systematic review.

BACKGROUND: The preconception period provides a unique opportunity to optimize the health of women and children. High rates of alcohol use and unintended pregnancies are common across many Western societies, and alcohol-exposed pregnancies (AEPs) are a possible unintended outcome. The aim of the current study was to evaluate preconception interventions for the prevention of AEPs. METHODS: A systematic search of four electronic databases (PubMed, Embase, CINAHL, and PsycINFO) was undertaken for relevant peer-reviewed articles published from 1970 onward. Studies were included if they enrolled women and/or their support networks during the preconception period. RESULTS: Nineteen studies met the inclusion criteria. The majority of studies (n = 14) evaluated CHOICES-based interventions, which incorporate motivational interviewing approaches to change alcohol and/or contraceptive behavior. The other five interventions included a range of different approaches and modes of delivery. The majority of interventions were successful in reducing AEP risk. Changes in AEP risk were more often driven by changes in contraceptive behavior, although some approaches led to changes in both alcohol and contraceptive behavior. CONCLUSIONS: The review indicated that many interventions were efficacious at reducing AEP risk during the preconception period through preventing unplanned pregnancy. The effectiveness estimated from these clinical trials may be greater than that seen in interventions when implemented in practice where there is a lack of blinding and greater attrition of participants during follow-up. Further research investigating the real-world effectiveness of these intervention approaches implemented across a wide range of clinical settings would be beneficial.

Alcohol Consumption during COVID among Women with an Existing Alcohol-Use Disorder.

Prior to the pandemic, our research team implemented a randomized controlled trial of an intervention to reduce risk for alcohol-exposed pregnancy (AEP) in American Indian women. When active recruitment for the in-person trial was paused due to COVID, the research team moved to conducting follow-up surveys with participants who had completed the intervention to better understand changes to their alcohol use during the pandemic. We collected surveys from 62 American Indian women who had completed the Native CHOICES intervention. Baseline data collected pre-COVID included demographics and scores on the Alcohol Use Disorders Identification Test (AUDIT). Follow-up surveys conducted during the active pandemic period included a self-reported questionnaire about changes in drinking patterns. At pre-COVID baseline, all participants were engaged in heavy or binge drinking. At follow-up during COVID, 24.2% reported drinking more, and over half had at least one binge drinking episode. Approximately half reported reduced drinking. We found that risky drinking remained an issue during the pandemic for many American Indian women who had engaged in this behavior pre-COVID, while others reported reducing their alcohol consumption. As the pandemic abates, concerted efforts must be made to reach those with identified alcohol use disorders to offer resources and intervention as needed.